Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): Preliminary results from KEYNOTE-173.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Peter Schmid ◽  
Yeon Hee Park ◽  
Eva Muñoz-Couselo ◽  
Sung-Bae Kim ◽  
Joohyuk Sohn ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Tumor Stage ◽  
End Points ◽  
Previously Treated ◽  
Ecog Ps ◽  
Dose Levels ◽  
Pathological Cr ◽  
Clinical Trial Information

556 Background: Pembro has shown efficacy and acceptable safety in pts with previously treated metastatic TNBC. The phase Ib KEYNOTE-173 study (NCT02622074) evaluated pembro + chemo as neoadjuvant therapy for locally advanced TNBC. We present cohorts A and B. Methods: Women aged ≥18 y with locally advanced, nonmetastatic TNBC; ECOG PS 0/1; and no prior chemo, targeted therapy, or immunotherapy within 12 mo were eligible. Dosing in A was single-dose pembro followed by 4 cycles of pembro Q3W + nab-paclitaxel (Np) weekly followed by 4 cycles of pembro + doxorubicin + cyclophosphamide Q3W. Dosing in B was the same as in A but with carboplatin Q3W added to pembro + Np. Concentrations were pembro 200 mg; doxorubicin 60 mg/m2; cyclophosphamide 600 mg/m2; Np 125 mg/m2 in A, 100 mg/m2 in B; and carboplatin AUC 6 (1 cycle = 21 d). DLTs were assessed at cycles 1-3 and 6-7. Dose levels were deemed toxic if ≥3 of the first 6 pts or ≥4 of 10 pts had DLTs. Surgery was 3-6 wk after treatment completion/discontinuation. Primary end points were safety and recommended phase 2 dose of pembro combined with chemo. Key efficacy end points were pathological CR (pCR) rate, defined as ypT0/Tis, ypN0, and ypT0 ypN0, and ORR (RECIST v1.1, investigator). pCR analyses included all pts. Results: By Jan 6, 2017, 10 pts were in each cohort. Median age was 53 y (range 32-71); most pts had invasive ductal histology (90%), primary tumor stage ≥T2 (90%), and nodal involvement (75%). DLTs (myelosuppression) occurred in 7 pts (3 in A, 4 in B) and were unrelated to pembro. Gr 3-4 treatment-related AEs (TRAEs) occurred in 8 pts in A and 10 pts in B; none were fatal. One pt in A and 2 pts in B discontinued for a TRAE (2 ALT elevations with pembro; 1 DVT with chemo). Overall ORR (CR+PR) before surgery was 80% (90% CI, 49-96) in A and 100% (90% CI, 74-100) in B. ypT0/Tis pCR rate was 70% (90% CI, 39-91) in A and 100% (90% CI, 74-100) in B; ypT0 ypN0 pCR rate was 50% (90% CI, 22-78) in A and 90% (90% CI, 61-100) in B; and yT0/Tis ypN0 pCR rate was 60% (90% CI, 30-85) in A and 90% (90% CI, 61-100) in B. Conclusions: Preliminary data suggest that pembro + chemo as neoadjuvant therapy for TNBC results in manageable toxicity and promising antitumor activity. Clinical trial information: NCT02622074.

Efficacy and safety of camrelizumab combined with FLOT versus FLOT alone as neoadjuvant therapy in patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16020-e16020
Author(s):  
Ning Liu ◽  
Zimin Liu ◽  
Yanbing Zhou ◽  
Zhaojian Niu ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Intraoperative Complications ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Tumour Regression ◽  
R0 Resection ◽  
Resection Rate ◽  
Tumour Regression Grade ◽  
Ecog Ps

e16020 Background: Docetaxel-based neoadjuvant chemotherapy has been suggested to be beneficial in patients with locally advanced gastric and gastro-oesophageal junction cancer (GC/GEJC). And immunotherapy also show promising treatment efficacy for advanced GC/GEJC. Here we compared the safety and efficacy of camrelizumab combined with chemotherapy versus chemotherapy alone as the neoadjuvant therapy for patients with resectable locally advanced GC/GEJC. Methods: Eligible patients diagnosed as resectable locally advanced GC/GEJC were randomized to receive neoadjuvant treatment, in arm A, the patients received FLOT alone (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², every 2 weeks), in arm B, the patients received FLOT combined with camrelizumab(camrelizumab 200mg intravenously every 3 weeks). Eligible patients underwent gastrectomy with D2 lymph node dissection. The primary end point of this trial was pCR rate and R0 resection rate, and the secondary end points were ORR,PFS, OS and safety profile. Results: From January 15 2020 to January 15 2021, 24 patients were recruited (11 patients in arm A and 13 patients in arm B). 19 patients had completed planned neoadjuvant treatment for 4 cycles (9 pts in the arm A, 10 ptsin the arm B). Two patients in the arm A were waiting for gastrectomy. This analysis was based on the 17 pts. In the arm A, the median age was 61 years (47-72 years) and a total of 5 males and 4 females, ECOG PS 0 (n = 1), ECOG PS 1 (n = 8). In the arm B, the median age was 63 years (57-71 years) and a total of 9 males and 1 females, all patients with ECOG PS 1. The R0 resection rate was high in arm B compared with arm A (10/10,100% vs. 5/7, 71.4%). No pCR were observed in the two arms. Tumour regression grade were as follows:TRG1 [arm A 0% (0/7), arm B 10% (1/10)], TRG2 [arm A 43% (3/7), arm B 60% (6/10)], TRG3 [arm A 29% (2/7), arm B 30% (3/10)].There was a significantly higher proportion of patients achieved a postoperative ypN0 in the arm B than arm A(60% vs 0%), which had preoperative clinical stage cT3-4N+M0. Postoperative pathologic staging was as follows: ypT1 [arm A 14% (1/7); armB 30% (3/10)]. ypT2 [armA 0% (0/7); armB 30% (3/10)]. ypT3 [arm A 29% (2/7); arm B 20% (2/10)]. ypT4 [armA 29% (2/7); armB 20% (2/10)]. Neither serious intraoperative complications nor immune-related adverse events were observed during perioperation. Treatment-related AEs neutropenia and leukopenia were manageable and there was no treatment-related death. Conclusions: Camrelizumab combined with FLOT showed promising efficacy as neoadjuvant treatment for patients with locally advanced gastric or GEJ adenocarcinoma, with low complications and acceptable toxicity. Clinical trial information: ChiCTR2000030610.

Neoadjuvant camrelizumab combined with chemotherapy and apatinib for locally advanced thoracic esophageal squamous cell carcinoma (ESCC): A single-arm, open-label, phase Ib study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4047-4047
Author(s):  
Zhen Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
End Points ◽  
Grade 3

4047 Background: Neoadjuvant therapy with PD-1 blockade plus chemotherapy has been found to be effective in the first-line treatment of advanced esophageal cancer. However, evidence of PD-1 blockade combined with chemotherapy as neoadjuvant treatment is limited. This study was designed to investigate the safety and efficacy of camrelizumab, a PD-1 blockade combined with chemotherapy and apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: A regiment of 2–4 cycles of neoadjuvant camrelizumab (200 mg, intravenous, day 1), nab-paclitaxel (150 mg/m2, intravenous, day 1), nedaplatin (50 mg/m2, intravenous, day 1), and apatinib (250 mg, orally, day 2–4) was given to the treatment-naive patients with resectable locally advanced ESCC. The treatments were repeated every 14 days. In this study, six patients were planned to receive two cycles of neoadjuvant therapy as safety assessment, and then 24 patients received four cycles of neoadjuvant therapy, followed by esophagectomy after 4–8 weeks. The primary end points were safety and feasibility. The secondary end points were the rate of major pathologic response (MPR) and pathologic complete response rate (pCR). Results: A total of 30 patients were enrolled, among them, five patients received two planned cycles of neoadjuvant therapy, and one patient missed the second cycle of therapy due to grade 3 ALT elevations. Further, all other 24 patients received four planned cycles of neoadjuvant therapy. A total of 11 patients (11/30, 36.7%) experienced grade 3 neoadjuvant treatment-related adverse events (TRAEs). No grade 4 and grade 5 TRAEs were reported. The most frequent grade 3 TRAEs was neutropenia (7/30, 23.3%). Twenty-nine patients underwent minimally invasive esophagectomy (McKeown procedure) after neoadjuvant therapy. The reason for not undergoing surgery was due to bone metastasis. There were five treatment-related surgical delays that were caused by adverse reactions (hyperglycemia, arthritis, anemia, leukopenia, capillary endothelial proliferation in oral mucosa). Among the 29 patients undergoing esophagectomy, 15 patients (15/29, 51.7%) achieved MPR, including 7 patients with pCR (7/29, 24.1%). Among the 24 patients who received four cycles of neoadjuvant treatment, there were 7 patients with pCR (7/24, 29.2%), and 14 patients with MPR (14/24, 58.3%). No surgery related mortality was documented. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy plus apatinib is a safe and tolerable treatment for patients with locally advanced ESCC, and the MPR and pCR rate are promising. Clinical trial information: ChiCTR1900023880.

Phase-II study of toripalimab combined with neoadjuvant chemotherapy for the treatment of resectable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Radiochemotherapy ◽  
Grade 3

e16029 Background: Compared with neoadjuvant chemotherapy alone，Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.

Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16033-e16033
Author(s):  
Jianqun Ma ◽  
Jinfeng Zhang ◽  
Yingnan Yang ◽  
Dayong Zheng ◽  
Xiaoyuan Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Radical Surgery ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Therapeutic Effects

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

Preliminary results of a randomized phase II study of paclitaxel and bevacizumab ± gemcitabine as first-line treatment for metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1089-1089
Author(s):  
K. L. Hoelzer ◽  
A. Brufsky ◽  
J. Hainsworth ◽  
J. T. Beck ◽  
R. Whorf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Efficacy And Safety ◽  
Randomized Phase Ii ◽  
Superiority Trial ◽  
Ecog Ps

1089 Background: The addition of bevacizumab (B) to paclitaxel (P) results in a significant improvement in PFS in pts with metastatic breast cancer (MBC) (Miller K, et al. New Engl J Med 2007). A randomized Phase II trial examining the efficacy and safety of adding gemcitabine (G) to the PB doublet has completed enrollment. Reported here are preliminary efficacy and safety results. Methods: This is a US, multicenter, randomized, superiority trial. Eligible pts have locally advanced or metastatic breast cancer, ECOG PS 0 or 1, and no prior cytotoxic therapy for metastatic disease. Prior adjuvant or neoadjuvant treatment with a taxane or endocrine therapy is allowed. Pts are randomized to receive P 90 mg/m2 on Days 1, 8, and 15, followed by B 10 mg/kg on Days 1 and 15 of a 28-day cycle, or the same regimen plus G 1,500 mg/m2 on Days 1 and 15. Primary endpoint is response rate according to RECIST criteria. Results: Between May 2006 and February 2008, 189 women were randomized to treatment. The table below summarizes currently available results. Grades 1–2 alopecia occurred in 28% of pts in the PB arm and in 38% of pts in the PB+G arm. One pt (2%) in the PB arm experienced a Grade 3 nosebleed. Grades 3 and 4 thrombotic events occurred respectively in 0% and 2% of pts in the PB arm, and in 3% and 2% of pts in the PB+G arm. Four pts (7%) in the PB arm and 3 pts (5%) in the PB+G arm discontinued due to treatment-related AEs. Three on-study deaths have occurred, none deemed related to study treatment. Conclusions: Study follow-up is ongoing. Full results will be available at the time of the meeting. Therapy with PB ± G is feasible and does not appear to be associated with significant bleeding or thrombotic events. As expected, the addition of G to the PB doublet appears to increase the incidence of neutropenia in pts with MBC. [Table: see text] [Table: see text]

A phase Ib trial of FOLFIRINOX plus saridegib, an oral hedgehog (Hh) inhibitor, in pts with advanced pancreatic cancer (PDAC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3105-3105 ◽  
Author(s):  
Andrew H. Ko ◽  
Noelle K. LoConte ◽  
Emily Kantoff ◽  
Robert W. Ross ◽  
Elizabeth G. Trehu ◽  
...  
Keyword(s):  
Trial Design ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Trial Design ◽  
Concurrent Administration ◽  
Phase Ib ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Levels

3105 Background: FOLFIRINOX has emerged as the optimal 1st-line treatment option for pts with advanced PDAC and good performance status; whether it can serve as the backbone upon which to add targeted agents in clinical trial design remains uncertain. The goal of this multicenter phase Ib study is to evaluate FOLFIRINOX in combination with saridegib, a novel oral agent that inhibits the Hh signaling pathway. In preclinical models of PDAC, saridegib increases chemotherapy delivery by depleting peritumoral stroma and increasing vascularity. Methods: Pts with previously untreated metastatic or locally advanced PDAC and ECOG PS 0-1 were eligible. Treatment consists of once-daily saridegib with concurrent administration of biweekly FOLFIRINOX (omitting the 5-FU bolus). A 3+3 dose escalation design was used (see dose levels below). Prophylactic WBC growth factor support is mandated.  DLT definitions include ALT/AST ≥10x ULN, grade 4 plts or ANC ≥5 d, or grade 3-4 nonheme toxicity. CT scans are obtained every 4 cycles. Limited PK analyses are performed. Results: Seven pts have been enrolled at the first 2 dose levels. Grade 1-2 AEs include GI (N/V/D), dehydration, fatigue, and LFT abnormalities. There was one DLT (grade 3 ALT elevation) at DL2. Other serious toxicities seen include grade 3 nausea (DL1) and grade 3 diarrhea (DL2). Tumor shrinkage has been observed in all 4 pts at DL1, ranging from 17-54%, with 2 unconfirmed PRs. Final MTD determination and updated safety and efficacy data will be presented at the meeting. Conclusions: A modified FOLFIRINOX regimen can be safely administered in combination with novel agents in clinical trials of PDAC. While saridegib was not beneficial when added to gemcitabine in a separate randomized phase II study, early evidence of significant responses on the current trial suggests that a more intensive chemotherapy platform may represent a preferable strategy in PDAC trial design. [Table: see text]

A phase I study of oral rucaparib in combination with carboplatin.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2586-2586 ◽  
Author(s):  
L Rhoda Molife ◽  
Patricia Roxburgh ◽  
Richard H. Wilson ◽  
Avinash Gupta ◽  
Mark R. Middleton ◽  
...  
Keyword(s):  
Phase I Study ◽  
Peritoneal Cancer ◽  
Platinum Sensitive ◽  
Dna Damaging Agents ◽  
Damage Repair ◽  
Recombination Repair ◽  
Proportional Increase ◽  
Ecog Ps ◽  
Dose Levels ◽  
Clinical Trial Information

2586 Background: Targeting poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA damage repair, may increase efficacy of DNA-damaging agents. This study evaluated the tolerability of oral rucaparib, a potent and selective PARP1/2 inhibitor, in combination with carboplatin (CP). Methods: Patients (pts) aged ≥18 with advanced solid tumors were included. Pts received lead-in doses of IV and oral rucaparib on Days -10 and -5, respectively, followed by CP on Day 1 and oral rucaparib on Days 1-14 q21 days. Treatment continued until disease progression. Pts with benefit could continue on rucaparib monotherapy once CP dosing was completed. Dose escalation was based on toxicities observed in Cycle 1 in cohorts of n=3-6. PK was assessed during Cycle 1. Results: 23 pts (median age 62 yrs [range 20 – 76]; 16 female; 9 ECOG PS=0; 6 ovarian/peritoneal cancer (OC), 5 breast cancer (BC), 2 NSCLC, 10 other tumor) were enrolled. Rucaparib doses of 80, 120, 180, 240, and 360 mg were administered with AUC3 CP, followed by 360 mg rucaparib with AUC4 CP, and currently with AUC5 CP. No DLTs have been reported. Median treatment cycles is 3 (range 1 – 15+). Treatment-related adverse events in ≥4 pts, all grades, include anemia (n=10), fatigue (n=9), nausea (n=7), thrombocytopenia (n=6), constipation (n=5), lethargy (n=5), neutropenia (n=5), and anorexia (n=4). One pt (OC, BRCAwt, AUC3 CP/180 mg rucaparib) had a PR of 5.1 mo duration. Two patients (both with OC; 1 BRCAunk, 1BRCAwt) discontinued CP (after 4 & 8 cycles) and continued on rucaparib monotherapy (additional 5 and 7+ cycles, respectively). An additional 4 pts (all BRCAunk) had stable disease (SD) >12 wks. Overall disease control rate (CR+PR+SD>12 wks) in OC pts across all dose levels was 50% (3/6). Dose-proportional increase in rucaparib exposure was observed with steady state achieved by Day 14 and mean t1/2of 15 h. Oral bioavailability was 38% and dose-independent. Rucaparib exposure was not changed by CP co-administration. Conclusions: The combination of oral rucaparib and CP is well tolerated and exhibits activity at clinically relevant doses of each agent. Further studies in platinum-sensitive and homologous recombination repair deficient populations are warranted. Clinical trial information: NCT01009190.

Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8008-8008 ◽  
Author(s):  
David R. Spigel ◽  
Scott N. Gettinger ◽  
Leora Horn ◽  
Roy S. Herbst ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Human Lung Cancer ◽  
Clinical Activity ◽  
Anti Cancer ◽  
Prior Surgery ◽  
Prior Systemic Therapy ◽  
Dose Levels ◽  
Clinical Trial Information

8008 Background: Human lung cancer expresses high levels of PD-L1, which may inhibit anti-cancer immune responses. MPDL3280A, a human monoclonal Ab containing an engineered Fc-domain designed to optimize efficacy and safety, targets PD-L1, blocking PD-L1 from binding its receptors, including PD-1 and B7.1. Methods: Pts with squamous or nonsquamous NSCLC received MPDL3280A IV q3w at doses between 1-20 mg/kg in a Ph I expansion study. Pts were treated for up to 1 y. Objective response rate (ORR) was assessed by RECIST v1.1. Reported ORR includes u/cCR and u/cPR. Results: As of Jan 10, 2013, 53 NSCLC pts were evaluable for safety and treated at doses of ≤1 (n=2), 10 (n=10), 15 (n=19) and 20 mg/kg (n=22). Pts had a median age of 61 y (range 24-83 y), 98% were PS 0-1, 89% had prior surgery and 55% had prior radiotherapy. 98% of pts received prior systemic therapy. Pts received treatment for a median duration of 106 days (range 1-324) of MPDL3280A. The incidence of all G3/4 AEs, regardless of attribution, was 34%, including pericardial effusion (6%), dehydration (4%), dyspnea (4%) and fatigue (4%). No G3-5 pneumonitis or diarrhea was reported. 37 NSCLC pts enrolled prior to Jul 1, 2012, were evaluable for efficacy. RECIST responses were observed at dose levels between 1 and 20 mg/kg, with all responses ongoing or improving. An ORR of 24% (9/37) was observed in pts with squamous and nonsquamous histologies, including several with rapid tumor shrinkage. Additional pts had delayed responses after apparent radiographic progression (not included in the ORR). The 24-week PFS was 48%. Analysis of biomarker data from archival tumor samples demonstrated a correlation between PD-L1 status and efficacy. Pts who were PD-L1 tumor status–positive showed an ORR of 100% (4/4) and a PD rate of 0% (0/4), while pts who were PD-L1 tumor status–negative showed an ORR of 15% (4/26) and a PD rate of 58% (15/26). Updated data will be presented. Conclusions: Treatment with MPDL3280A was well tolerated, with no pneumonitis-related deaths. Rapid and durable responses were observed. PD-L1 tumor status correlated with response to MPDL3280A. Clinical trial information: NCT01375842.

Ramucirumab (R) plus pembrolizumab (P) in treatment naive and previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: A multi-disease phase I study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4046-4046 ◽  
Author(s):  
Ian Chau ◽  
Johanna C. Bendell ◽  
Emiliano Calvo ◽  
Rafael Santana-Davila ◽  
Hendrik-Tobias Arkenau ◽  
...  
Keyword(s):  
Median Duration ◽  
Gastroesophageal Junction ◽  
Survival Rates ◽  
Kidney Injury ◽  
Primary Objective ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

4046 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the tumor microenvironment. Methods: Ongoing, multi-cohort, phase 1a/b trial enrolled pts with G/GEJ adenocarcinoma, measurable disease, ECOG PS 0-1, previously treated (Cohorts A and B) or untreated (Cohort A2) for advanced disease. PD-L1 was positive (tumor proportion score [TPS] ≥1%) or negative (TPS < 1%) using the DAKO PD-L1 22C3 IHC pharmDx assay. R was administered at 8 mg/kg on Days 1&8 (Cohorts A and A2) or 10 mg/kg on Day 1 (Cohort B) with P 200 mg on Day 1 q3W. Primary objective- assess safety and tolerability of R+P; preliminary efficacy will be examined. Results: As of 21-Nov-2016, 41 previously treated G/GEJ pts were enrolled. Median age was 58 y, 76% male, 66% had ECOG PS of 1, 46% were PD-L1+, and 59% received study treatment as third or subsequent line. Median duration on therapy was 2.8 mo and 4.1 mo for A and B, respectively. Overall, 33 (80%) pts experienced a treatment-related AE (TRAE) and similar between cohorts A and B. Ten (24%) pts experienced grade 3-4 TRAEs, most commonly colitis (7%) and hypertension (7%). One treatment-related death occurred (pneumonitis and pulmonary sepsis). Responses occurred in 3 (7%) pts with 46% disease control rate (DCR). Progression-free and overall survival rates at 6 mo were 22.4 % (95% CI, 9.8-38.0) and 51.2% (95% CI, 33.9-66.1) respectively. Nine (22%) pts remain on treatment. Eighteen of 25 planned treatment naïve G/GEJ pts were enrolled. Median age was 70 yr, 83% male, 56% had ECOG PS of 0, and PD-L1 status is pending. Median duration on therapy was 2.1 mo. Twelve (67%) pts experienced a TRAE. Grade 3 TRAEs occurred in 5 (28%) pts (hypertension [n = 3], diarrhea, and acute kidney injury). No grade 4-5 events occurred. Preliminary efficacy data showed 3 (17%) pts responded with 50% DCR. Median PFS is immature and 89% of pts remain on treatment. Conclusions: R+P generated no new safety signals and demonstrated encouraging antitumor activity in treatment naïve and previously treatedadvanced G/GEJ adenocarcinoma. Clinical trial information: NCT02443324.

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